Nifev150 mg

Nifev is a multi-target tyrosine kinase inhibitor approved for specific fibrotic lung conditions and, in combination therapy, certain lung cancers. Approved/established indications include:

• Idiopathic pulmonary fibrosis (IPF): FDA-approved to slow decline in lung function in adults with IPF.
• Chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype: FDA-approved for adults whose ILD, of various underlying causes, is progressing despite standard management.
• Systemic sclerosis-associated interstitial lung disease (SSc-ILD): FDA-approved to slow the rate of decline in pulmonary function in adults with scleroderma-related ILD.

Combination/adjunct use:

• Locally advanced, metastatic, or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma histology: used in combination with docetaxel, after first-line chemotherapy, in a number of countries; this combination indication may not be approved in every market, so local labeling should be confirmed.

Nifev should not be used for lung diseases or cancers outside these approved settings and should only be prescribed by a physician experienced in managing these conditions.

Each soft gelatin capsule of Nintedanib contains nintedanib (as nintedanib esylate) equivalent to 100 mg or 150 mg of nintedanib base. The capsule fill also contains excipients including soya lecithin, medium-chain triglycerides, and hard fat, within a gelatin shell with printing ink.

Because the capsule contains soya lecithin, Nintedanib must not be used in patients with known hypersensitivity to peanut or soya.

Nifev is an orally administered, small-molecule tyrosine kinase inhibitor that blocks multiple receptors involved in blood vessel growth and fibrotic tissue remodeling. It is supplied as soft gelatin capsules (100 mg and 150 mg) taken twice daily. Nifev was developed both as an antifibrotic agent for progressive lung fibrosis and, in a different dosing and combination regimen, as an antiangiogenic agent for certain lung cancers.

Nifev belongs to the therapeutic class of multi-target tyrosine kinase inhibitors (angiokinase inhibitors), used as an antifibrotic and antineoplastic agent.

Nintedanib is a small-molecule, intracellular inhibitor that competitively binds to the adenosine triphosphate (ATP)-binding pockets of three receptor tyrosine kinase families:

• Vascular endothelial growth factor receptors (VEGFR 1-3)
• Fibroblast growth factor receptors (FGFR 1-3)
• Platelet-derived growth factor receptors (PDGFR alpha and beta)

Nintedanib also inhibits non-receptor tyrosine kinases such as Lck, Lyn, and Src. By blocking these pathways, Nintedanib interrupts signaling cascades that drive fibroblast proliferation, migration, and differentiation into myofibroblasts in fibrotic lung tissue, and inhibits angiogenesis that supports tumor growth. Nintedanib is well absorbed after oral administration, extensively bound to plasma proteins (about 97-98%), metabolized primarily by ester hydrolysis with subsequent glucuronidation, and eliminated mainly via the biliary/fecal route, with an elimination half-life of approximately 10-15 hours.

Nifev capsules should be taken orally with food, swallowed whole with a glass of water. Do not open, chew, or crush the capsules, as this may alter drug absorption and increase the risk of local mucosal irritation. Doses should be spaced approximately 12 hours apart, at approximately the same times each day.

Nifev is a substrate of P-glycoprotein (P-gp) and, to a lesser extent, CYP3A4. Clinically significant interactions include:

• Strong P-gp/CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir): may significantly increase Nifev plasma concentrations, raising the risk of adverse effects; use with caution and monitor closely, or avoid the combination.
• Strong P-gp/CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, St. John's wort): may significantly decrease Nifev exposure and reduce efficacy; avoid concurrent use if possible.
• Anticoagulants and antiplatelet agents (e.g., warfarin, heparin, aspirin, clopidogrel): concurrent use with Nifev increases the risk of bleeding; monitor closely (see Precautions and Warnings).

Inform the prescriber of all other medicines, supplements, and herbal products being used before starting Nifev.

The most common side effect of Nifev is diarrhea, occurring in more than half of treated patients and occasionally requiring dose adjustment or antidiarrheal treatment. Other common side effects include:

• Nausea and vomiting
• Abdominal pain and decreased appetite
• Liver enzyme (transaminase) elevation
• Headache
• Weight loss
• Hypertension

Serious but less common effects include hepatotoxicity, gastrointestinal perforation, bleeding events, and arterial thromboembolic events (see Precautions and Warnings). Patients should promptly report severe or persistent diarrhea, yellowing of the skin or eyes, unusual bleeding or bruising, or severe abdominal pain while taking Nifev.

Nifev can cause fetal harm and is not recommended during pregnancy, based on animal studies showing embryo-fetal toxicity and its antiangiogenic mechanism of action. Women of reproductive potential must use effective (barrier) contraception during treatment with Nifev and for at least 3 months after the last dose. If pregnancy occurs during treatment, the patient should inform her physician immediately so the potential risk to the fetus can be assessed. Nifev should be used in pregnancy only if there is no alternative and only if the potential benefit, in the treating physician's judgment, justifies the potential risk.

It is not known whether Nifev passes into human breast milk. Because of the potential for serious adverse effects in a nursing infant, breastfeeding is not recommended during treatment with Nifev and for at least a few days after the final dose. A physician should be consulted regarding infant feeding options.

Nifev carries several serious risks that require monitoring:

• Hepatotoxicity: Liver function tests (ALT, AST, bilirubin) should be checked before starting Nifev, periodically during the first months of treatment, and as clinically indicated. Dose reduction, interruption, or discontinuation may be needed if liver enzymes rise significantly.
• Gastrointestinal perforation: Use with caution in patients with recent abdominal surgery, prior GI perforation, active peptic ulcer disease, or diverticular disease. Discontinue Nifev immediately if perforation occurs.
• Bleeding: Nifev has antiangiogenic activity and may increase the risk of bleeding, including major bleeding events. Use with caution in patients with a known bleeding risk or those on anticoagulant/antiplatelet therapy.
• Arterial thromboembolic events: Use with caution in patients with a history of ischemic heart disease or stroke; discontinue if an acute event occurs.
• Wound healing complications: Nifev may impair wound healing. Treatment should be interrupted for at least a few weeks before elective surgery and resumed only after adequate wound healing, at the physician's discretion.
• Diarrhea: May be severe and lead to dehydration and electrolyte imbalance; early antidiarrheal treatment and adequate hydration are recommended.

Patients should be counseled to promptly report new or worsening symptoms and to attend all scheduled monitoring visits while taking Nifev.

There is limited clinical experience with overdose of Nifev. Based on its known effects, overdose may increase the risk and severity of gastrointestinal symptoms, such as diarrhea, nausea, and vomiting, and liver function abnormalities. There is no specific antidote for Nifev overdose. If overdose is suspected, seek immediate medical attention or contact a poison control center; treatment should be supportive, with interruption of Nifev and symptomatic management as directed by a physician.

Store at room temperature (below 30°C), in the original blister/container, away from light and moisture. Keep out of reach of children.

Renal impairment: No dose adjustment is required in patients with mild to moderate renal impairment; Nifev has not been well studied in severe renal impairment or end-stage renal disease, so caution is advised.

Hepatic impairment: Dose reduction to 100 mg twice daily is required in mild impairment (Child-Pugh A); Nifev is not recommended in moderate to severe hepatic impairment (Child-Pugh B or C).

Elderly: No overall differences in safety or efficacy have been observed based on age alone, but elderly patients should be monitored closely for adverse effects, particularly diarrhea and bleeding risk.

Low body weight/ethnicity: Patients with low body weight (under 45 kg) or of certain ethnic backgrounds may have higher drug exposure and should be monitored closely for adverse effects.

Pediatric patients: Safety and efficacy of Nifev have not been established in children.

Nifev for pulmonary fibrosis and ILD indications is generally intended for long-term, continuous use, since it slows disease progression rather than curing the underlying condition. Treatment is typically continued indefinitely as long as the patient tolerates it and continues to derive benefit, under regular physician review. For the NSCLC combination indication, Nifev is continued in cycles alongside docetaxel until disease progression or unacceptable toxicity occurs. Any decision to stop or interrupt Nifev should be made in consultation with the prescribing physician.

Tyrosine kinase inhibitor (angiokinase inhibitor); antifibrotic agent; antineoplastic agent

Nintedanib works by blocking the intracellular signaling of VEGFR, FGFR, and PDGFR tyrosine kinase receptors, key drivers of fibroblast activity and blood vessel formation. By inhibiting these pathways, Nintedanib reduces the proliferation and migration of fibroblasts in fibrotic lung disease and suppresses tumor angiogenesis in cancer, thereby slowing disease progression.

The safety and efficacy of Nifev have not been established in pediatric patients. Nifev is approved for use in adults only, and its use in children or adolescents is not recommended outside of a clinical trial setting.